PROJECT SUMMARY-ANIMAL CORE B The mission of our Perimenopause in Brain Aging and Alzheimer's Disease Program Project (P3) is to discover biological transformations in brain that occur during the perimenopausal transition that lead to endophenotypes predictive of risk for Alzheimer's disease (AD). Our goals are to identify the mechanisms by which these transformations occur and to translate these discoveries into strategies to prevent conversion to an at-Alzheimer's-risk phenotype. The proposed program of research builds on our discovery of the perimenopausal bioenergetic transition in brain and its predictive association with cognitive decline in postmenopausal women to investigate the impact of the APOE4 allele on this uniquely female aging experience. Outcomes of our mechanistic to clinical to global population program of research could provide insights into the increased burden of the ApoE4 gene and risk of AD in ApoE4 positive women. The mission of Animal Core (Core B) is to ensure the success of the Perimenopause Program Project through provision of animals as needed to Projects 1?2. To achieve its mission, the Animal Core will extend previously developed rodent models of perimenopause and menopause to humanized ApoE4 and ApoE3 rodent mice and rat models; maintain and track animals from acquisition or birth, determination of cycling status and perimenopausal transition, randomized study enrollment, experimental manipulation, to tissue collection across the entire Perimenopause Program Project; and obtain blinded tissue samples for analyses by Analytic Core and/or Projects.